The principal objectives of this proposal are to evaluate the role played by H-2-linked genes in controlling immune responsiveness to Heligmosomoides polygyrus in the mouse, to map the H-2-linked genes involved, and to conduct comparative immunological studies between genetically characterized resistant and susceptible strains of mice in order to identify the functional effectors of immunity against this parasite. The objectives will be addressed by studying infections in H-2 congenic strains of mice which differ only at genes within the major histocompatibility complex, and in strains of mice which share common H-2-linked genes but express different genetic backgrounds. We will compare systemic and local antibody responses to H. polygyrus in resistant and susceptible strains of mice using a parasite-specific enzyme-linked immunosorbent assay (ELISA) for IgG, IgM, IgA, and IgE antibody, and will compare antibody production potential by testing selected lymphoid cell populations in plaque forming cell (PFC) assays after both in vivo and in vitro (Mishell-Dutton) antigen priming. The cells involved in these responses will be characterized by inhibiting or eliminating specific functional cell types from these cultures using antisera specific for the H-2, Ia, and Ly antigens expressed on functional subsets of immunocompetent cells. We will also use these antisera to characterize the cell populations responsible for the marked suppression of antibody responsiveness exhibited by susceptible but not resistant strains of infected mice. In addition to studying the humoral immune responses to H. polygyrus, we will study cellular immune responses in genetically characterized resistant and susceptible strains of mice. The cell populations controlling the marked L3 dose-dependent splenomegaly exhibited by resistant but not susceptible strains of mice will also be characterized. We will then quantitate cellular responses to both larval and adult H. polygyrus antigens using a sensitive and specific ear swelling assay as well as by in vitro lymphocyte stimulation assays. Finally, we will determine if the cellular or humoral immune response in susceptible strains of mice is specifically suppressed during H. polygyrus infection. This will be accomplished by selective depletion of suppressor cells from the host by injection of antisera specific for I-J coded gene products or from cell cultures using specific Ia and Ly antisera.